Prasugrel for the treatment of patients with acute coronary syndrome
Filippo Marzot, Vittorio Pengo
Clinical Cardiology, Thrombosis Centre, University of Padua, Italy
Abstract: Prasugrel (CS-747, LY640315) is a novel member of the thienopyridine class of oral anti-platelet agents (also including ticlopidine and clopidogrel). Like other thienopyridines, prasugrel is a prodrug that is inactive in vitro. Prasugrel’s conversion to its active metabolite is more rapid and efficient than that of other thienopyridines, with a less strict dependence on specific cytochrome P-450 enzymes. Prasugrel’s active metabolite (R-138727) binds specifically and irreversibly to the platelet P2Y12 purinergic receptor, thus inhibiting ADP-mediated platelet activation and aggregation. Preclinical data and early clinical data in healthy subjects showed greater platelet inhibition and consistency with prasugrel as opposed to clopidogrel. Clinical studies in patients with cardiovascular disease confirmed the greater efficacy of prasugrel compared with clopidogrel. Collectively, these phase 1/1b studies and a phase 2 study (JUMBO-TIMI 26) aided in dose selection for the phase 3 trial (TRITONTIMI 38) in patients with acute coronary syndrome undergoing percutaneous coronary intervention. This trial once again confirmed the greater anti-platelet effect of prasugrel, but also highlighted a higher risk of bleeding, even fatal. Another phase 2 trial (PRINCIPLE-TIMI 44) compared prasugrel and high-dose clopidogrel in patients undergoing cardiac catheterization for planned PCI.
Keywords: prasugrel, oral antiplatelet agents, acute coronary syndrome
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF]